THU0215 IGM ANTIBODIES AGAINST MALONDIALDEHYDE AND PHOSPHORYLCHOLINE IN DIFFERENT SYSTEMIC RHEUMATIC DISEASES
Authors: Divya Thiagarajan, Susanna Lundström, Roman Zubarev, Jitong Sun, Marta Alarcon-Riquelme, Johan Frostegård
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> IgM antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) may have protective properties in cardiovascular or rheumatic diseases including SLE and RA.<sup>1-4</sup> Little is known about their role in other systemic rheumatic conditions. <h3>Objectives:</h3> The objective is to compare different rheumatic conditions in relation to these antibodies, and also clinical outcome, with focus on cardiovascular disease. We also aim to characterize them and compare them by use of proteomics. <h3>Methods:</h3> IgM anti-PC and anti-MDA was measured using ELISA in patients with SLE (374), RA (354), Mixed connective tissue disease (MCTD, 77), Systemic sclerosis (SSc, 331), Sjögren's syndrome (SjS, 324), primary antiphospholipid syndrome (PAPs, 65), undifferentiated connective tissue disease (UCTD, 118) and 515 matched healthy controls (HC). Cardiovascular score (CV) was broadly defined based on clinical disease symptoms. Anti-PC and anti-MDA peptide/protein characterization were compared using a proteomics de novo sequencing approach. IgM anti-MDA and anti-PC were extracted from total IgM. The proportion of Treg cells was determined by flow cytometry. <h3>Results:</h3> The maximal difference between cases and controls was shown for MCTD: significantly lower IgM Anti-PC but not anti-MDA among patients (median 49.3RU/ml vs 70.4 in healthy controls, p(t-test)=0.0037). Low levels (below 25th percentile) of anti-PC but not anti-MDA were significantly more prevalent in MCTD, SLE, SjS and SSc. The IgM anti-PC variable region profiles were distinctly different and also more homologous in their content than anti-MDA. Anti-PC but not anti-MDA were significantly negatively correlated with CV in the whole patient group. In contrast to IgM anti-PC, IgM anti-MDA did not promote polarization of Tregs. <h3>Conclusion:</h3> Anti-PC could be a protection marker for MCTD and also for SLE, SjS and SSc while anti-MDA did not differ. anti-PC level is negatively correlated with CV in the patient group cohort. These findings could have both diagnostic and therapeutic implications, one possibility being active or passive immunization with PC. <h3>References:</h3> [1] Frostegard J. Immunity, atherosclerosis and cardiovascular disease. BMC Med. 2013;11:117. [2] Anania C, Gustafsson T, Hua X, Su J, Vikstrom M, de Faire U, Heimburger M, Jogestrand TandFrostegard J. Increased prevalence of vulnerable atherosclerotic plaques and low levels of natural IgM antibodies against phosphorylcholine in patients with systemic lupus erythematosus. Arthritis Res Ther. 2010;12:R214. [3] Rahman M, Sing S, Golabkesh Z, Fiskesund R, Gustafsson T, Jogestrand T, Frostegård AG, Hafstrom I, Liu Aand Frostegård J. IgM antibodies against malondialdehyde and phosphorylcholine are together strong protection markers for atherosclerosis in systemic lupus erythematosus: Regulation and underlying mechanisms. Clin Immunol. 2016;166-167:27-37. [4] Ajeganova S, Fiskesund R, de Faire U, Hafstrom Iand Frostegard J. Effect of biological therapy on levels of atheroprotective antibodies against phosphorylcholine and apolipoproteins in rheumatoid arthritis - a one year study. Clin Exp Rheumatol. 2011;29:942-50. <h3>Acknowledgement:</h3> Preciseads Clinical Consortium <h3>Disclosure of Interests:</h3> Divya Thiagarajan: None declared, Susanna Lundström: None declared, Roman Zubarev: None declared, Jitong Sun: None declared, Marta Alarcon-Riquelme: None declared, Johan Frostegård Shareholder of: Minor shareholder and inventor in startup-company Athera Biotechnologies, but they do not produce drugs yet and rheumatology is not in their focus.